Iron Deficiency Anemia
Conditions
Keywords
Iron deficiency anemia, Feraheme, ferumoxytol, iron sucrose, Venofer, IDA
Brief summary
The purpose of the study is to evaluate the efficacy and safety of intravenous (IV) ferumoxytol compared to IV iron sucrose for the treatment of iron deficiency anemia (IDA).
Interventions
DRUGFerumoxytol
IV Ferumoxytol
DRUGIron Sucrose
IV Iron Sucrose
Sponsors
AMAG Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria include: 1. Males and females ≥18 years of age 2. Participants with IDA defined as having: 1. Hemoglobin \<10.0 g/deciliter (dL) 2. Transferrin saturation (TSAT) \<20% 3. Participants who have a history of unsatisfactory oral iron therapy or in whom oral iron cannot be used 4. Female participants of childbearing potential who are sexually active must be on an effective method of birth control for at least 1 month prior to screening and agree to remain on birth control until completion of participation in the study Key
Exclusion criteria
include: 1. History of allergy to IV iron 2. Allergy to two or more classes of drugs 3. Participants on dialysis or with an estimated glomerular filtration rate \<30 mL/minute(min)/1.73 square meter (m\^2) 4. Female participants who are pregnant, intend to become pregnant, are breastfeeding, within 2 weeks postpartum, or have a positive serum/urine pregnancy test 5. Hemoglobin ≤7.0 g/dL 6. Serum ferritin \>600 nanogram/mL
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants Who Achieved A ≥2.0 g/dL Increase In Hemoglobin At Any Time From Baseline To Week 5 | Baseline (Day 1) through Week 5 | Participants who achieved a ≥2.0 g/dL increase in hemoglobin at any time from Baseline up to Week 5 are presented. Increase in hemoglobin at any time from Baseline up to Week 5 was calculated for each participant based on: Hemoglobin Change = Hemoglobin (Week X) - Hemoglobin (Baseline), where Week X was any post-Baseline visit up to and including Week 5. Baseline was defined as the Day 1 value (prior to injection of study drug). The screening or most recent value prior to Day 1 was used for any participant with missing Day 1 information. Participants with no post-Baseline hemoglobin values were classified as not achieving a ≥2.0 g/dL increase. Statistical analysis was performed for data up to Week 5 only. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change In Hemoglobin From Baseline To Week 5 | Baseline (Day 1), Week 5 | Mean change in hemoglobin from Baseline to Week 5 was calculated for each participant as: Hemoglobin Change = Hemoglobin (Week 5) - Hemoglobin (Baseline). Baseline was defined as the Day 1 value (prior to injection of study drug). The screening or most recent value prior to Day 1 was used for any participant with missing Day 1 information. If the Week 5 hemoglobin value was missing, the change from Baseline was imputed to be zero. |
| Participants Achieving A Hemoglobin Level ≥12.0 g/dL At Any Time From Baseline To Week 5 | Baseline (Day 1) through Week 5 | Participants who achieved a ≥12.0 g/dL hemoglobin level at any time from Baseline up to Week 5 are presented. Increase in hemoglobin at any time from Baseline up to Week 5 was calculated for each participant based on: Hemoglobin Change = Hemoglobin (Week X) - Hemoglobin (Baseline), where Week X was any post-Baseline visit up to and including Week 5. Baseline was defined as the Day 1 value (prior to injection of study drug). The screening or most recent value prior to Day 1 was used for any participant with missing Day 1 information. Participants without any post-Baseline hemoglobin values were treated as non-responders. |
| Mean Change In TSAT From Baseline To Week 5 | Baseline (Day 1), Week 5 | Mean change in TSAT from Baseline to Week 5 was calculated for each participant as: TSAT Change = TSAT (Week 5) - TSAT (Baseline). Baseline was defined as the Day 1 value (prior to injection of study drug). The screening or most recent value prior to Day 1 was used for any participant with missing Day 1 information. If the Week 5 TSAT value was missing, the change from Baseline was imputed to be zero. |
| Mean Change In Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score From Baseline To Week 5 | Baseline (Day 1), Week 5 | The FACIT-Fatigue questionnaire is a 13 item questionnaire designed and validated to specifically assess the presence and impact of treatment on fatigue and related symptoms, such as tiredness, on health-related quality of life in anemic participants with cancer. The questionnaire has 13 items, each measured on a 4-point Likert scale. Scoring ranges from 0 (the most fatigued) to 52 (the least fatigued) points, with higher scores representing better functioning or less fatigue. Mean change in FACIT-Fatigue Score from Baseline to Week 5 was calculated for each participant as: FACIT-Fatigue Score Change = FACIT-Fatigue Score (Week 5) - FACIT-Fatigue Score (Baseline). Baseline was defined as the Day 1 value (prior to first dose of study drug).The screening or most recent value prior to Day 1 was used for any participant with missing Day 1 information. If the Week 5 FACIT-Fatigue Score value was missing, the change from Baseline was imputed to be zero. |
| Time To Hemoglobin Increase Of ≥2.0 g/dL Or Hemoglobin Value Of ≥12.0 g/dL From Baseline | From Baseline (Day 1) up to Week 5 | The time to hemoglobin increase of ≥2.0 g/dL or hemoglobin value of ≥12.0 g/dL was defined as the days from Baseline (Day 1) to the first time the participant had an increase in hemoglobin of ≥2.0 g/dL or hemoglobin value of ≥12.0 g/dL, and was calculated using a Kaplan-Meier curve. Participants who did not have a hemoglobin increase of ≥2.0 g/dL or to a hemoglobin level ≥12.0 g/dL were censored at their last visit day. Participants without any post-Baseline study visits were not included. |
Countries
Australia, France, Germany, Hungary, Italy, Latvia, Lithuania, Poland, Romania, South Africa, South Korea, Spain, Ukraine, United Kingdom
Participant flow
Recruitment details
The study was open to enrollment for adult participants with iron deficiency anemia (IDA), defined as hemoglobin \<10.0 grams (g)/deciliter (dL) and transferrin saturation (TSAT) \<20%, and a history of unsatisfactory oral iron therapy or in whom oral iron could not be used.
Participants by arm
| Arm | Count |
|---|---|
| Ferumoxytol Participants received a total of 2 doses of IV ferumoxytol 510 mg (17 mL). The first IV 510 mg dose was administered on Day 1 (Baseline) and second dose 2 to 8 (5±3) days after the first dose, for a total cumulative dose of 1.02 g. | 406 |
| Iron Sucrose Participants received an IV injection or infusion of iron sucrose 200 mg (10 mL) on Day 1 (Baseline) and on 4 other non-consecutive days over a 14-day period for a total cumulative dose of 1.0 g. Participants receiving their first ever exposure to IV iron sucrose, received a test dose on Day 1 prior to receiving the remainder of the first dose, as prescribed in the package insert for some countries. | 199 |
| Total | 605 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Other-Medical monitor request | 1 | 0 |
| Overall Study | Other-Participant request | 2 | 0 |
| Overall Study | Other-Personal reasons | 2 | 0 |
| Overall Study | Other-Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 10 | 6 |
Baseline characteristics
| Characteristic | Ferumoxytol | Iron Sucrose | Total |
|---|---|---|---|
| Age, Continuous | 48.0 years STANDARD_DEVIATION 14.89 | 48.9 years STANDARD_DEVIATION 14.66 | 48.2 years STANDARD_DEVIATION 14.81 |
| Sex: Female, Male Female | 342 Participants | 160 Participants | 502 Participants |
| Sex: Female, Male Male | 64 Participants | 39 Participants | 103 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 95 / 406 | 69 / 199 |
| serious Total, serious adverse events | 17 / 406 | 5 / 199 |
Outcome results
Primary
Participants Who Achieved A ≥2.0 g/dL Increase In Hemoglobin At Any Time From Baseline To Week 5
Participants who achieved a ≥2.0 g/dL increase in hemoglobin at any time from Baseline up to Week 5 are presented. Increase in hemoglobin at any time from Baseline up to Week 5 was calculated for each participant based on: Hemoglobin Change = Hemoglobin (Week X) - Hemoglobin (Baseline), where Week X was any post-Baseline visit up to and including Week 5. Baseline was defined as the Day 1 value (prior to injection of study drug). The screening or most recent value prior to Day 1 was used for any participant with missing Day 1 information. Participants with no post-Baseline hemoglobin values were classified as not achieving a ≥2.0 g/dL increase. Statistical analysis was performed for data up to Week 5 only.
Time frame: Baseline (Day 1) through Week 5
Population: ITT Population: Any randomized participant who had any exposure to study drug (ferumoxytol or iron sucrose) and was based upon randomized treatment assignment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ferumoxytol | Participants Who Achieved A ≥2.0 g/dL Increase In Hemoglobin At Any Time From Baseline To Week 5 | Up to Week 3 | 291 Participants |
| Ferumoxytol | Participants Who Achieved A ≥2.0 g/dL Increase In Hemoglobin At Any Time From Baseline To Week 5 | Up to Week 4 | 327 Participants |
| Ferumoxytol | Participants Who Achieved A ≥2.0 g/dL Increase In Hemoglobin At Any Time From Baseline To Week 5 | Up to Week 5 | 341 Participants |
| Iron Sucrose | Participants Who Achieved A ≥2.0 g/dL Increase In Hemoglobin At Any Time From Baseline To Week 5 | Up to Week 3 | 117 Participants |
| Iron Sucrose | Participants Who Achieved A ≥2.0 g/dL Increase In Hemoglobin At Any Time From Baseline To Week 5 | Up to Week 4 | 145 Participants |
| Iron Sucrose | Participants Who Achieved A ≥2.0 g/dL Increase In Hemoglobin At Any Time From Baseline To Week 5 | Up to Week 5 | 162 Participants |
Comparison: Participants who achieved a ≥2.0 g/dL increase in hemoglobin from Baseline up to Week 5 were analyzed. Statistical comparison was performed for data up to Week 5 only.~Baseline was defined as the Day 1 value (prior to injection of study drug). The screening or most recent value prior to Day 1 was used for any participant with missing Day 1 information.p-value: 0.283395% CI: [-3.89, 9.06]Cochran-Mantel-Haenszel
Secondary
Mean Change In Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score From Baseline To Week 5
The FACIT-Fatigue questionnaire is a 13 item questionnaire designed and validated to specifically assess the presence and impact of treatment on fatigue and related symptoms, such as tiredness, on health-related quality of life in anemic participants with cancer. The questionnaire has 13 items, each measured on a 4-point Likert scale. Scoring ranges from 0 (the most fatigued) to 52 (the least fatigued) points, with higher scores representing better functioning or less fatigue. Mean change in FACIT-Fatigue Score from Baseline to Week 5 was calculated for each participant as: FACIT-Fatigue Score Change = FACIT-Fatigue Score (Week 5) - FACIT-Fatigue Score (Baseline). Baseline was defined as the Day 1 value (prior to first dose of study drug).The screening or most recent value prior to Day 1 was used for any participant with missing Day 1 information. If the Week 5 FACIT-Fatigue Score value was missing, the change from Baseline was imputed to be zero.
Time frame: Baseline (Day 1), Week 5
Population: ITT Population: Any randomized participant who had any exposure to study drug (ferumoxytol or iron sucrose) and was based upon randomized treatment assignment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ferumoxytol | Mean Change In Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score From Baseline To Week 5 | 13.1 units on a scale | Standard Deviation 11.78 |
| Iron Sucrose | Mean Change In Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score From Baseline To Week 5 | 12.4 units on a scale | Standard Deviation 11.22 |
Secondary
Mean Change In Hemoglobin From Baseline To Week 5
Mean change in hemoglobin from Baseline to Week 5 was calculated for each participant as: Hemoglobin Change = Hemoglobin (Week 5) - Hemoglobin (Baseline). Baseline was defined as the Day 1 value (prior to injection of study drug). The screening or most recent value prior to Day 1 was used for any participant with missing Day 1 information. If the Week 5 hemoglobin value was missing, the change from Baseline was imputed to be zero.
Time frame: Baseline (Day 1), Week 5
Population: ITT Population: Any randomized participant who had any exposure to study drug (ferumoxytol or iron sucrose) and was based upon randomized treatment assignment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ferumoxytol | Mean Change In Hemoglobin From Baseline To Week 5 | 2.9 g/dL | Standard Deviation 1.62 |
| Iron Sucrose | Mean Change In Hemoglobin From Baseline To Week 5 | 2.7 g/dL | Standard Deviation 1.3 |
Secondary
Mean Change In TSAT From Baseline To Week 5
Mean change in TSAT from Baseline to Week 5 was calculated for each participant as: TSAT Change = TSAT (Week 5) - TSAT (Baseline). Baseline was defined as the Day 1 value (prior to injection of study drug). The screening or most recent value prior to Day 1 was used for any participant with missing Day 1 information. If the Week 5 TSAT value was missing, the change from Baseline was imputed to be zero.
Time frame: Baseline (Day 1), Week 5
Population: ITT Population: Any randomized participant who had any exposure to study drug (ferumoxytol or iron sucrose) and was based upon randomized treatment assignment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ferumoxytol | Mean Change In TSAT From Baseline To Week 5 | 15.7 percentage of saturation | Standard Deviation 16.8 |
| Iron Sucrose | Mean Change In TSAT From Baseline To Week 5 | 11.9 percentage of saturation | Standard Deviation 14.41 |
Secondary
Participants Achieving A Hemoglobin Level ≥12.0 g/dL At Any Time From Baseline To Week 5
Participants who achieved a ≥12.0 g/dL hemoglobin level at any time from Baseline up to Week 5 are presented. Increase in hemoglobin at any time from Baseline up to Week 5 was calculated for each participant based on: Hemoglobin Change = Hemoglobin (Week X) - Hemoglobin (Baseline), where Week X was any post-Baseline visit up to and including Week 5. Baseline was defined as the Day 1 value (prior to injection of study drug). The screening or most recent value prior to Day 1 was used for any participant with missing Day 1 information. Participants without any post-Baseline hemoglobin values were treated as non-responders.
Time frame: Baseline (Day 1) through Week 5
Population: ITT Population: Any randomized participant who had any exposure to study drug (ferumoxytol or iron sucrose) and was based upon randomized treatment assignment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ferumoxytol | Participants Achieving A Hemoglobin Level ≥12.0 g/dL At Any Time From Baseline To Week 5 | Up to Week 3 | 123 Participants |
| Ferumoxytol | Participants Achieving A Hemoglobin Level ≥12.0 g/dL At Any Time From Baseline To Week 5 | Up to Week 4 | 210 Participants |
| Ferumoxytol | Participants Achieving A Hemoglobin Level ≥12.0 g/dL At Any Time From Baseline To Week 5 | Up to Week 5 | 271 Participants |
| Iron Sucrose | Participants Achieving A Hemoglobin Level ≥12.0 g/dL At Any Time From Baseline To Week 5 | Up to Week 3 | 33 Participants |
| Iron Sucrose | Participants Achieving A Hemoglobin Level ≥12.0 g/dL At Any Time From Baseline To Week 5 | Up to Week 4 | 67 Participants |
| Iron Sucrose | Participants Achieving A Hemoglobin Level ≥12.0 g/dL At Any Time From Baseline To Week 5 | Up to Week 5 | 96 Participants |
Secondary
Time To Hemoglobin Increase Of ≥2.0 g/dL Or Hemoglobin Value Of ≥12.0 g/dL From Baseline
The time to hemoglobin increase of ≥2.0 g/dL or hemoglobin value of ≥12.0 g/dL was defined as the days from Baseline (Day 1) to the first time the participant had an increase in hemoglobin of ≥2.0 g/dL or hemoglobin value of ≥12.0 g/dL, and was calculated using a Kaplan-Meier curve. Participants who did not have a hemoglobin increase of ≥2.0 g/dL or to a hemoglobin level ≥12.0 g/dL were censored at their last visit day. Participants without any post-Baseline study visits were not included.
Time frame: From Baseline (Day 1) up to Week 5
Population: ITT Population: Any randomized participant who had any exposure to study drug (ferumoxytol or iron sucrose) and was based upon randomized treatment assignment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Ferumoxytol | Time To Hemoglobin Increase Of ≥2.0 g/dL Or Hemoglobin Value Of ≥12.0 g/dL From Baseline | 23.1 days |
| Iron Sucrose | Time To Hemoglobin Increase Of ≥2.0 g/dL Or Hemoglobin Value Of ≥12.0 g/dL From Baseline | 25.2 days |